Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006849 (oral candidiasis)
 1,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV predominantly infects the CD4+ T cells, which during the progression of the disease are eliminated, causing an immune deficiency which renders the patients more susceptible to infections. To evaluate the relevance of the CD4+ T cell elimination and thus the clinical usefulness of CD4/CD8 subset determinations in HIV infected persons, we investigated whether analyses of 667 subset determinations of 365 patients correlated with clinical stages of HIV-infection (CDC classification). Progress of HIV related disease was accompanied by a fall in CD4+ cells and an increase in CD8+ cells, leading to a drastically reduced CD4/CD8 ratio. This change of T-cell subset values correlated well with the clinical classification (CDC). It was, however, only statistically significant if percent values were used, but not if absolute CD4 cell counts, calculated from the peripheral lymphocyte count, were considered. While patients in CDC stage IVC2 (mainly Candida stomatitis) did not differ from stages IIB, IIIB, IVA, we found statistically lower CD4 values if the patients had stage IVA plus IVC2. Stage IVC1 (mainly Pneumocystis carinii pneumonia [PcP, n = 20]) had even lower CD4 values, as PcP appeared almost exclusively in patients with CD4 counts below 20% or 200/microliter. The lowest CD4 counts were observed in patients with Kaposi sarcoma (n = 11) with CD4 cells less than 10% and significant elevated values of CD8 cells (greater than 50%). While the total lymphocyte count correlated with the absolute counts of CD4 and CD8 cells, it was impossible to estimate the T-subset distribution from the absolute lymphocyte count. Our investigations show that a decreased number of circulating CD4 cells correlates well with an increased tendency to develop infections, and thus support the relevance of CD4 cell measurements for the optimal care of asymptomatic HIV infected persons in particular. They also show that the percent values correlate better with clinical stage than the absolute CD4 cell count.
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PMID:[Relationship between T-subsets and clinical aspects of HIV-associated diseases]. 167 35

The purpose of this study was to examine the antitumor activity, toxic effects, and plasma pharmacokinetics of fractionated doses of oral etoposide aiming at the achievement of prolonged safe and active plasma drug levels in patients with AIDS-related Kaposi sarcoma (KS). This was designed as a phase II trial in which consecutive patients with progressing AIDS-KS after at least 3 months of active antiretroviral therapy received oral etoposide at the dose of 20 mg/m2 every 8 hours daily for 7 days every 21 days, with the study of its plasma pharmacokinetics. Eligible patients were 18 to 60 years old, with a histopathologically confirmed diagnosis of AIDS-related KS, human immunodeficiency virus-positive test, progressing after at least 3 months of active antiretroviral therapy, World Health Organization (WHO) performance status 0 to 3, New York University staging IIA or greater, no active infection except oral candidiasis, normal bone marrow, liver, and renal function, and who signed an informed consent. Objective tumor responses were evaluated after at least one full treatment course according to a modified WHO criteria, and toxicity was evaluated weekly and graded using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) criteria. For the pharmacokinetic study, plasma was obtained from patients during the first drug administration immediately before and at various time points thereafter. Etoposide was measured after extraction from plasma by a standard high-performance liquid chromatography. Twenty-one patients were accrued for the study, and 18 of them met the eligibility criteria. They were all men, with median age of 36 years old (range: 25-50 years), median WHO performance status 0 (range: 0-3) median CD4+ count (cells/mm3) 67 (range: 8-443), prior AIDS diagnosis in 10 of 18 cases, NYU staging IIA (1 patient), IIB (1), IIIA (7), IIIB (1), IVA (4), and IVB (4) sites of disease: mucocutaneous only (5), mucocutaneous/lymph nodes (5), mucocutaneous/lung (5) and mucocutaneous/lymph nodes/lung (2); and prior cytotoxic treatment in two patients. Seventy-two percent of cases presented some form of toxic effect (NCI-CTC). Leukopenia was documented in 50% of cases, anemia occurred in 61%, whereas thrombocytopenia was documented in 17% of the patients. The main nonhematologic toxicities were nausea and vomiting in 17% of cases and alopecia in 44%. The overall objective response rate was 83%, with 2 complete remissions documented (11%). The median duration of responses was 12 weeks (range: 3-45 weeks). The median t1/2 of etoposide in plasma was 4.11 hours (range: 1.95-9.64), area under the curve was 13.51 microg/h/ml (range: 7.12-24.42), Cmax was 2.17 microg/ml (1.40-4.41), tmax (1.00-2.00), mean residence time 4.62 hours (range: 3.75-5.20 hours), CIt (total clearance) 3.13 l/m2/h (range: 1.49-5.20 l/m2/h), Vd 13.08 l/m2 (range: 6.23-19.65 l/m2), and the median etoposide plasma concentration time greater than 1 microg/ml was 3.69 hours (range: 1.00-6.80 hours). The use of fractionated oral daily doses of etoposide produced significant antitumor activity with manageable clinical toxicity in the individuals with AIDS-KS included in this trial. This more favorable therapeutic index of etoposide could be due to the achievement of more sustained plasma levels of the drug within safe but active concentrations.
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PMID:Fractionated doses of oral etoposide in the treatment of patients with aids-related kaposi sarcoma: a clinical and pharmacologic study to improve therapeutic index. 1131 95